The introduction of high-density DNA micro-arrays has significantly reduced the time and cost for DNA detection through miniaturization and automation that are made available by some advanced IC fabrication technologies. The dominant DNA micro-array based detection systems rely on fluorescence or radioactive methods to discriminate matched (ie hybridized) and unmatched (unhybridized) DNA samples for a given testing probe. Referring to FIG. 1, conventionally, a solid support (eg a DNA array chip) 10 with DNA probes 12 is provided as shown in FIG. 1(a). It is to be noted that this DNA “chip” is not related to a packaged integrated circuit device which is also called a “chip”. The sample DNA fragments 14 typically have one or more fluorescent labels. The sample DNA fragments 14 are applied to the DNA array chip 10. If any of the sample DNA fragments 14 match the DNA probes 12, the DNA fragments 14 with the fluorescence label are captured or bound by the DNA probes 12, which is called hybridization as shown in FIG. 1(). If the DNA fragments 14 do not match the probes 12, the DNA fragments 14 are washed away by the subsequent cleaning steps and no fluorescence will be associated with those unmatched DNA probes on the DNA array chip 10. To detect the matching of DNA sample 14 with the probes 12, an expensive UV light source 16 is usually required to excite the fluorescence label as shown in FIG. 1(c). In addition, the detection is either based on microscope, or photographic system that can detect color. Thus, the process is relatively expensive and inconvenient. Further, such conventional method requires specific color filters that are composed of very complicated film structure. Finally, the fluorescence and radioactive signal intensity degrade with time and can cause large variations in the sampled data, such that the testing result might be unreliable.
Instead of fluorescent labels, nano-metallic particles can be used as labels. Compared with the fluorescence based detection method, a nano-particle based DNA detection method has the advantages of: (1) physical properties (such as conductivity and opacity) that are easier to be electronically detected; (2) signal is stable with time; (3) fewer external components needed. These 3 advantages lead to more consistent experimental results. Some previous work using the conducting property of the metal particles has been proposed but it requires modifications to the CMOS process to include inert metal (such as gold or platinum) and different surface passivation techniques. Also it is difficult to process the conduction data using noise reduction techniques.
It is therefore the object of the present invention to provide an improved detection method and detector for test samples, particularly biological samples such as proteins and nucleic acids.